The atomic force microscope (AFM) is becoming increasingly useful for studying ultra-structure and functional properties of biological molecules and tissue. The DBEPS Instrumentation Research and Development Resource is strengthening the AFM capabilities at NIH to support the diverse needs of IC scientific projects. An AFM instrument system has been obtained and is being adapted to allow measurements to be made of biological samples. A perfusion chamber has been developed to enable a single cell to be retained for examination and permitting manipulation of the extra-cellular environment. Using DBEPS expertise in optics, electronics, mechanical design, and other areas, associated instrumentation and quantitative analysis methods are being pursued to advance AFM technology and apply it to solve novel biomedical problems. Collaborative intramural biological projects include the investigation of the viscoelastic energetics of the protein clathrin and its assemblies that are important to subcellular protein trafficking (NICHD) and surface modified protein interaction dynamics (NIDDK). Integration of AFM with near-field scanning optical microscopy (NIAID) is being pursued through a collaborative agreement with NIST to develop and adapt existing instrumentation for application to biological problems.